CD40 Engagement Enhances Antigen-Presenting Langerhans Cell Priming of IFN-γ-Producing CD4+ and CD8+ T Cells Independently of IL-12
| Autor: | Robert L. Fairchild, Anton V. Gorbachev |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
T cell Immunology Antigen-Presenting Cells Priming (immunology) CD8-Positive T-Lymphocytes Biology Dermatitis Contact Lymphocyte Activation Mice Interleukin 21 Cell Movement medicine Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor CD40 Antigens Antigen-presenting cell Antigen Presentation ZAP70 Antibodies Monoclonal Interferon-alpha Flow Cytometry Interleukin-12 Molecular biology medicine.anatomical_structure Langerhans Cells CD8 Signal Transduction |
| Zdroj: | The Journal of Immunology. 173:2443-2452 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The delivery of CD40 signaling to APCs during T cell priming enhances many T cell-mediated immune responses. Although CD40 signaling up-regulates APC production of IL-12, the impact of this increased production on T cell priming is unclear. In this study an IL-12-independent T cell-mediated immune response, contact hypersensitivity (CHS), was used to further investigate the effect of CD40 ligation on the phenotypic development of Ag-specific CD4+ and CD8+ T cells. Normally, sensitization for CHS responses induces hapten-specific CD4+ T cells producing type 2 cytokines and CD8+ T cells producing IFN-γ. Treatment of mice with agonist anti-CD40 mAb during sensitization with the hapten 2,4-dinitrofluorobenzene resulted in CHS responses of increased magnitude and duration. These augmented responses in anti-CD40 Ab-treated mice correlated with increased numbers of hapten-specific CD4+ and CD8+ T cells producing IFN-γ in the skin draining lymph nodes. Identical results were observed using IL-12−/− mice, indicating that CD40 ligation promotes CHS responses and development of IFN-γ-producing CD4+ and CD8+ T cells in the absence of IL-12. Engagement of CD40 on hapten-presenting Langerhans cells (hpLC) up-regulated the expression of both class I and class II MHC and promoted hpLC migration into the T cell priming site. These results indicate that hpLC stimulated by CD40 ligation use a mechanism distinct from increased IL-12 production to promote Ag-specific T cell development to IFN-γ-producing cells. |
| Databáze: | OpenAIRE |
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